Several methodological limitations make it difficult to investigate in randomised, controlled studies whether antidepressants affect (increase or decrease) suicidality. Different kinds of studies (epidemiological, quasi-experimental intervention, naturalistic follow-up, etc.) should therefore also be considered in order to obtain the most comprehensive evidence. Taken together, these different approaches supply reasonable evidence that antidepressants are able to reduce both suicidal ideation and suicide in depressive patients. Data on suicide attempts are not robust enough to draw clear conclusions. Even though there are no consistent indications from the different study types of a suicidality-inducing effect of SSRIs or antidepressants in adults in general, the principle possibility of such an adverse effect in single cases or in subgroups of patients should be considered carefully. Different mechanisms could principally lead to suicidality-enhancing effects, for example the pharmacological mode of action related to different transmitter systems, to special pharmacodynamic properties like activating/drive-enhancing effects or to side effects like akathisia. Special dispositions of patients, i.e. personality disturbances such as borderline personality disorder, comorbidity, non-response, bipolarity and other factors, should be considered. In everyday clinical practice the discussion about the possible risks of the SSRIs or antidepressants in general should not result in clinicians forgetting the benefits of these drugs, especially their lower lethal toxicity profile. This is a great advantage, especially in cases with severe suicidality where the choice of a less toxic antidepressant helps to avoid the risk of fatality if the patient should misuse the antidepressant for a suicide attempt.

Patients for whom the diagnosis of depression was established, yet did not respond to adequate treatment are defined as suffering from resistant depression (RD). As 20-30% of depression is resistant, depression subtypes with distinct pathophysiology are considered.

The neurobiological approach to RD aims to identify and characterize these subtypes. Different underlying mechanisms which may play a role in RD include: tolerance (“escape”), a “kindling” type of phenomenon, or no response to begin with. There are several types of underlying pathophysiological mechanisms proposed for RD, including: HPA axis hyperactivity, thyroid abnormality, estrogen in postmenopausal women, lower availability of l-tryptophan to the brain, frontal or parietal perfusion defects, genetic factors, thyroidal abnormalities, a combination of 5HT/HPA axis and brain lesion, 5HT, NA and HPA abnormalities, sleep abnormalities and immunological factors.

In order to gain better knowledge of these mechanisms, studies of RD patients providing a careful evaluation of the HPA axis and of serotonergic and noradrenergic responsivity, as well as evaluation of the thyroid system, are warranted. Tryptophan depletion and NE depletion have proven to be effective tools in the study of depression and might be of particular interest in RD. Brain imaging, pre- and post-treatment, and a dichotomous comparison of changes in brain activity in patients who responded to treatment for RD might be of value. However, these have not yet been studied systematically.

Patients with RD suffer greatly and need to be treated. Various underlying psychobiological abnormalities might assist us in tailoring treatment especially to the patient.

This workshop aims to make progress in the knowledge of the cognitive symptoms and her evaluation in the psychotic diseases. Schizophrenia begins in late adolescence causing a derailment of social, educational, and occupational pursuits that extends to the end of life. The psychosocial costs contribute to the extraordinary public health care costs of this illness. Alleviation of the positive symptoms, negative symptoms, depression, and anxiety is insufficient to restore psychosocial status. An improvement in social, educational, and occupational status is dependent on improvement in cognitive status.

Primary Prof. JE Rojo & O. Pino will emphasize the relevant aspects of the neuropsychological evaluation in clinical practice, and relationships between cognitive, clinical, psychosocial status and social performance in patients with psychosis dysfunction.

Although vital to prognosis, cognitive status is often neglected in clinical practice because neuropsychological assessments are expensive and time consuming, and they require considerable expertise. The Screen for Cognitive Impairment in Psychiatry (SCIP) is a 10 to 15 minute assessment of cognitive status developed to encourage routine assessment of cognitive status in clinical practice, and to promote research on the alleviation of cognitive impairments in psychiatric illness. Prof. Purdon will briefly review the rational for a brief assessment of cognitive status. He will present evidence supporting the comparability of three alternate forms of the SCIP from three Canadian normative samples and one large clinical sample. He will also present evidence supporting the validity of the brief screening tool relative to a comprehensive assessment of neuropsychological status in a large sample of psychiatric inpatients. The primary objective will be to encourage the use of the SCIP in routine clinical practice.

Afterwards, Prof. P. McKenna try to describe the new research strategies and methods of investigation in neuropsychology and schizophrenia, the state of art more novelty and relevant.

From 1987 to 2002, I followed nine women who killed their baby newborn and nearly ninety women who denied their pregnancy or their delivery in Paris area. A comparison between the clinical findings of the two groups led me to identify prevention strategy at a prenatal stage:

1. Detecting harmful thoughts towards the baby before birth

Among the women who denied or concealed their pregnancy some revealed having negative or violent impulse thoughts against the foetus after the end of pregnancy denial. Some also displayed suicidal impulse thoughts. These harmful thoughts decreased after they spoke out past traumatic sexual abuse, especially if the foetus was the result of rape.

2. Listening and planning the delivery time

Some were not able to content their thoughts and act out them in beating up their abdomen and consequently the foetus. They felt so guilty they avoided planning the delivery time as a consequence. Some have killed their child because they were afraid to explain this to healthcare professionals. They denied the birth and delivered alone.

3. Offering an anonymous welcome if they wish to do so

I observed that to welcome with anonymity before birth increased their care for the future of the newborn.

The parental killing of children in the first year after birth, the infanticide, constitutes a complex phenomenon, that seldom occurs. Infanticide has been reported across numerous cultures and throughout history. Children in the first year of life have the highest Risk of becoming a victim of filicide. Studies on infanticide show that mothers who kill their children are frequently psychiatrically disturbed. Depressive as well as psychotic symptoms are with high frequency related to the newborn or to the maternity itself. Although depression is the most common postpartum disorder and may represent a vital danger for the mother and the child. The association between the psychiatric disorder and the infanticide will be usually explained through the maternal psychopathological symptoms. The bonding to the child hasn't often been seen as a central motivational cause for an infanticide. The present case report underlines the importance of a postpartum bonding disorder and its relation to a higher infanticide risk for the child.

Since opening in 1863 Broadmoor Hospital, in Crowthorne, Berkshire, 30 miles west of London, has admitted or readmitted over 2000 women. This is a tiny proportion of the women who have been incarcerated in prison over this time, but the level of public interest and ethical issues involved in their care, far outweighs the number of cases. Their stories and reasons for admission are of great interest and complexity.

At first infanticide was the usual offence resulting in admission, but with increasing knowledge of the causes and consequences of mental illness, and new legislation to deal with it, reasons for admission became much more varied. Arson became the commonest reason for admission in recent years. Also, over the last 40 years, those admitted are younger and stay for a shorter time.

The treatment of the disturbed and often tragic women patients in Broadmoor has also changed. Primitive surgery and blunderbuss drug regimes have evolved into multidisciplinary practices and widely varied therapies.

Political pressure groups campaigning against the admission of mentally ill women to high security hospitals have succeeded in changing government policy. Three high security units in England will be reduced to one, accommodating only the most dangerous women. The rapidly growing range of public and private medium security units will treat all other women detained under the Mental Health Act.

This is a time of change in the treatment of mentally abnormal women offenders in England. It presents an opportunity for those of us who care about these women to share knowledge and experience with professionals from other countries.

The main objective of this research is to present the results of a study about the relations between health and the acts of violence towards women.

They were chosen important institutions in the Health Care instalment in 18 districts of the Portuguese Continent.

The results now presented, correspond to a long and unceasing psycho-sociological investigation amongst women with 18 and more years that had been in those institutions back in 2003 what resulted in 2300 inquiries.

The results had allowed us to make a comparative analysis between women whose manifestations of illness to the physical and psychological level could be related with the acts of violence of that they had been victims and those that, having similar manifestations, had not been victims.

We have tried to obtain descriptive and comprehensive models of the types of illness and it's relation with the violent acts, as well as the psycho-socio-cultural conditions where they had occurred.

This study will be able to constitute a support instrument to the decision and action of the agents involved in this domain. To the definition of politics level, to the implementation of promotion measures of health and prevention of illness, in order to contribute for the improvement of the quality of life of those women.

The results not only represent an increase in the Health knowledge but are also able to give us an idea of the socio-cultural complexity that are in the base of the violence against women.

There is large evidence that stress plays a crucial role in the pathophysiology and course of many psychiatric disorders. The stress-vulnerability model has been widely accepted for many years. Hypothalamic-pituitary-adrenal (HPA) axis dysregulation has been previously reported in schizophrenia. Patients in the acute phase of the disease seem to have an activated HPA axis (Holsboer-Trachsler et al. 1997) compared to patients who are clinically stable. Results from studies on ACTH regulation are inconsistent. abnormal dexamethasone suppression test (DST) results have been shown in normal aging, depression and schizophrenia. DST non-suppression was associated with cognitive impairment, ventricular enlargement and poorer prognosis (for review: Yeap and Thakore, 2005). Long-term hippocampal exposure to excessive levels of glucocorticoids can induce cognitive dysfunctions due to reduced neuronal volume of this limbic structure. the pharmacological reduction of glucocorticoid excess may help to improve cognitive functioning in schizophrenia.

Therapeutic Drug Monitoring (TDM) is a useful tool to survey individual patients for the correct prescription and dosing of neuroleptic drugs. Confounders for causal drug effect relations are both patient-related and drug-related. An example of a patient-related confounders is problems with compliance to prescribed medication that can be objectively identified or ruled out by TDM in cases of non-response or partial but insufficient clinical response. This problem may arise both in the acute phase of treatment as well as during long-term treatment. Examples of combined patient-related and drug-related confounders are the very individual pharmacokinetic (PK) handling of the drug once the patent has ingested a neuroleptic compound. All such drugs undergo significant metabolism in the body, which is subjected to major inter-individual variability to a large extent due to existence of polymorphic genetic expressions among enzymes responsible for drug detoxification processes in the liver. Moreover, each separate neuroleptic compound, whether its is a classical or an atypical agent, has different affinities for these drug catabolic enzymes. The entire picture of PK-variability existing for antipsychotic drugs is therefore in healthy young male volunteers about one order of magnitude. In real life, i.e. in the everyday naturalistic clinical setting where for example also polypharmacy is a common feature, this variation in the PK between individuals increase 10-fold to be about two orders in magnitude.

This presentation focus TDM-studies where PK-variability and drug PK-effect relations for traditional as well as atypical antipsychotic agents are scrutinized.

Uncertainties in individual response to specific antipsychotics are a major limitation in improving treatment. Pharmacogenetics offers the opportunity to help the clinical decision process by allocating individuum-specific odds for response versus non-response. Pharmacogenetics in schizophrenia has up to now produced only a very limited number of valid results. A main reason might be the heterogeneity of samples under study and lack by standardization of treatment (e.g. mixture of first onset and chronic patients).

The German Competence Network of Schizophrenia has completed a long-term treatment protocol in first-episode patients with schizophrenia (double-blind randomized study with risperidone versus haloperidol). We explored the predictive power of disease-associated variants in disposition genes and modifier genes for schizophrenia. We detected predictive markers in the genes for dysbindin, neuregulin 1 and COMT. These variants were also associated with neuropsychological correlates of schizophrenia.

Thus we can be confident that time has come to improve the tools for prediction of response to antipsychotics.

The pharmacotherapeutic approach to the treatment of major depression consists in giving an optimal dose of an antidepressant medication for a sufficient time. Using this conventional strategy in standard medication trials, approximately half the patients present a response, defined as a 50% improvement, but only about 30-40% generally achieves remission. This is a poor treatment outcome and these numbers have been questioned the patient population tested may be different from those in regular ambulatory conditions. The STAR*D project addressed the latter concern by treating patients all comers, including patients with physical and psychiatric co-morbidities, first with a SSRI and then with switch and combination approaches. Not covered in STAR*D was the strategy of adding an atypical antipsychotic in SSRI-resistant patients. Finally, a novel strategy consists in using two antidepressant medications from treatment initiation.

All the available evidence from randomised controlled studies indicates that antipsychotic medications substantially reduce the risk of relapse in the stable phase of illness. The lowest dose should be chosen at which preferably no side effects occur, the risk of relapse seems to be optimally reduced and, if symptoms are still present, suppression of these is optimised. Side effects have to be assessed and, if necessary, pharmacotherapy has to be adjusted. Despite several methodological design issues, second-generation antipsychotics have proven similar or superior efficacy in preventing relapse and suppression (or even improvement) of symptoms compared to FGAs (available studies of the specific agents supply evidence for periods of up to 2 years). Due to the decreased risk of EPS, especially tardive dyskinesia, and, as observed in most studies, the superior efficacy in improving negative, cognitive and depressive symptoms together with at least comparable (for some agents, e.g., risperidone, olanzapine, superior) efficacy in relapse prevention, second-generation antipsychotics should be preferred in long-term treatment. Given all the known problems in compliance and discontinuation, which were underlined by the CATIE study, depot preparations should be considered for optimum effectiveness in preventing relapse. Randomised, control-group studies to determine the advantages of depot preparations of atypical neuroleptics compared to depots of typical neuroleptics are still lacking. The target strategy in long-term treatment of schizophrenia should be a combination of long-term antipsychotic treatment and psycho- and sociotherapeutic procedures, so that the relapse rate is further reduced and the course of disease can be further improved.

There is a need for long-term treatment of unipolar depression. With the older medication, tricyclic antidepressants, acute treatment was possible, but unfortunately, the patients did not take the long-term medication, specifically in the correct dosage. With the introduction of modern antidepressants, this dilemma has been partly solved, as the patients are more willing to take their medication. However, compliance studies indicate that this is only the case for a very low percentage. The European Health Regulatory authorities (EMEA) demand for every antidepressant introduced into the market to demonstrate efficacy for at least 6 months. These requirements are not necessary for the American counterpart, the Food and Drug Administration (FDA). Therefore, all the modern medications demonstrate this efficacy, a few of them even for a longer period. The question arises if this benefit can also be achieved for children and adolescents as well as for the elderly. Just a few studies suggest this also for the younger and older population. Side effects as well as the failure of understanding the nature of unipolar depression limit the necessary long-term usage of antidepressants. Education programmes, which indicate that depression is a disease like hypertension, asthma or diabetes, help the patients understand the disease and the triggers, which might accompany the long-term outcome.

During the lecture the unmet needs for treatment of unipolar depression as well as modern outcome studies of recently introduced medication will be presented.

Bipolar depression, and particularly its long-term treatment, represents a challenge nowadays. Although mania and hypomania are the distinctive mood disturbances in bipolar disorder, it is becoming increasingly apparent that depression is the predominant mood alteration in bipolar disorder, and the main cause of dysfunction and mortality for patients. However, despite the clear clinical and public health implications of these facts, research has traditionally neglected bipolar depression, and clinicians continue to encounter many difficulties in the management of patients. Lithium and anticonvulsants, with the exception of lamotrigine, appear to be more effective in mania than in depression. Antidepressants, particularly tricyclics and dual acting compounds, may induce mania, especially when used in the absence of an antimanic drug. The evidence on this safety concern is less compelling as far as SSRIs are concerned. Changes in dopaminergic activity have been implicated in the pathogenesis of bipolar depression and now two apparently opposite strategies are being used to improve depressive symptoms in bipolar patients: adjunctive dopamine agonists, such as pramipexole, or dopamine antagonists, such as atypical antipsychotics. Three recent placebo-controlled studies support the use of olanzapine, and particularly quetiapine, in the treatment of bipolar depressed patients. Electroconvulsive therapy remains as an option in treatment-resistant patients. Cognitive-behavioral therapy and psychoeducation seem much better for the prevention of relapse than for the treatment of acute episodes. Further studies are ongoing to test novel strategies for the long-term treatment of bipolar depression.

Anxiety disorders, including panic disorder (PD), generalized anxiety disorder, and social anxiety disorder (SAD), generally have a chronic course.

Based on clinical experience, experts recommend that effective treatment be continued for at least 12 months. Only in the recent years, randomized long-term and relapse prevention studies with a duration of 24-52 weeks have been conducted to establish sustained efficacy of drug treatment, triggered by the requirements of the regulatory authorities. Now, an expanding body of evidence from controlled trials demonstrates the long-term efficacy and tolerability of the serotonin selective reuptake inhibitors (SSRIs) such as escitalopram, fluvoxamine, paroxetine, or sertraline, the serotonin norepinephrine reuptake inhibitor (SNRI) venlafaxine, the calcium channel modulator pregabalin, the reversible inhibitor of MAO-A moclobemide and other drugs for the long-treatment of anxiety disorders.

All these studies confirm the necessity of continuous treatment over at least several months, as differences to placebo were still observable after treatment over half a year. Generally, the drugs were tolerated well during maintenance therapy. In the long-term treatment of anxiety disorders the same doses are usually prescribed as in the acute treatment phase.

There is also evidence for the effectiveness of cognitive-behavioral therapy (CBT). CBT and drug treatment can be combined, and at least for panic disorder, synergistic effects have been observed.

There is a long-recognized association between alcohol consumption and aggressive behaviour. This study was designed to examine aggression in a group of socially well-adapted recovered alcoholics (RA). The question adressed was whether the treatment, together with long-term abstinence from alcohol, could reduce aggression and hostility in RA.

A group of male RA (n = 64), who did not meet the DSM-IV criteria for any psychiatric or personality disorder, were recruited to the study from aftercare groups. According to data from their group therapists, they were reliably abstinent for at least 3 years and socially well adapted. The study participants representing the control group (n = 69), diagnosed as being “reliable nonalcoholics” (NA) by the Munich Alcoholism Test, were recruited from general practice. Data were derived from an in-house questionaire on general characteristics of both groups, and aggressive and hostility traits were assessed using Buss-Durkee Hostility Inventory (BDHI). The univariate and multivariate between-groups design was used for data analysis.

Taking into account the BDHI dimensions of aggression and hostility, the difference between RA and NA groups was statistically significant (Wilks' lambda (8,125)=0.769; p=0.00004). There were statistically significant differences in the BDHI scales for indirect aggression, irritability, negativism, suspicion, resentment, and guilt. Both RA and NA group did not differ significantly in variables that assessed physical and verbal aggression. After a 3-year abstinence, subjects from the RA group displayed signs of hostility and covert aggression.